SUMMARY Anyone who has ever suffered a common cold knows that both taste and smell contribute to our experience of food. Understanding how smell and taste interact to ultimately drive food choice will make a major impact on our understanding of disorders that are typically characterized by abnormal food choice, most notably obesity and diabetes. The neural mechanisms underlying taste-smell interactions, however, remain largely unknown, and are the focus of the present proposal. The proposed work follows directly from existing behavioral and neuro- physiological data. Behavioral work has demonstrated an influence of taste on smell in flavor preference for- mation. Recent work from our own lab has identified a potential neural substrate for mediating the influence of taste on smell by demonstrating that primary olfactory cortex (OC) receives gustatory input via primary gustatory cortex (GC). Using rats as a model system, the present proposal will combine naturalistic multisensory stimulus presentation, optogenetics and electrophysiological recordings in the context of a flavor preference learning task to investigate the role of interactions between the primary gustatory and olfactory systems in mediating multi- sensory flavor preference learning. Specific Aim 1 will use anatomical tracing, optogenetic manipulation of GC neuron axon terminals in OC, and electrophysiological mapping experiments to dissect the systems- and circuit- level organization of gustatory input to OC. Preliminary data suggest the existence of monosynaptic projections from GC to OC. Specific Aim 2 will then record activity from single OC neurons in response to uni- and multi- sensory flavor stimuli to characterize convergence and integration of flavor-related gustatory and olfactory input. Preliminary data suggest that taste and smell inputs to OC are integrated through functional, spatial and temporal convergence on single OC neurons. Specific Aim 3 will place the network relaying gustatory input to OC in the context of a taste-mediated flavor preference learning task to determine the causal role GC?OC projections in modulating odor representations and forming flavor preferences. Preliminary data suggest that multisensory ex- perience induces lasting changes in OC odor responses. The results obtained from these experiments will pro- vide novel insight into how OC functions in a natural, behaviorally-relevant multisensory context, specifically uncovering the mechanisms underlying taste-smell interactions in flavor perception and preference formation.